Public Release: 

Ledipasvir-sofosbuvir combination proves effective in subset of patients with chronic hepatitis C

Simple, ribavirin- and interferon-free, all-oral regimen provides new treatment option for people with hepatitis C, genotypes 4 and 5E

European Association for the Study of the Liver

April 24, 2015, Vienna, Austria: A new study presented today at The International Liver Congress™ 2015 has demonstrated that ledipasvir (LDV) in combination with sofosbuvir (SOF) achieves sustained virologic response rates 12 weeks after treatment (SVR12; primary endpoint), of 93% and 95% in patients chronically infected with hepatitis C virus (HCV) genotypes 4 or 5, respectively.

In the study, LDV/SOF was administered in a once-daily, fixed-dose combination tablet for 12 weeks to treatment-naive and treatment-experienced patients with or without cirrhosis. A total of 85 patients were enrolled in the study: 44 patients had GT-4 and 41 patients had GT5 chronic HCV infection. SVR12 rates were similar across all patient types.

HCV GT-4 is estimated to account for 8% to 13% and GT-5 for about 1% of all chronic HCV infections globally. Clinical studies evaluating the treatment outcome with new direct-acting antiviral agents in GT-4 and especially GT-5 HCV infection have been limited, to date.

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LEDIPASVIR/SOFOSBUVIR TREATMENT RESULTS IN HIGH SVR RATES IN PATIENTS WITH CHRONIC GENOTYPE 4 AND 5 HCV INFECTION

Armand Abergel* 1, Veronique Loustaud-Ratti2, Sophie Metivier3, Deyuan Jiang4, Kathryn Kersey4, Steven J. Knox4, Philip S. Pang4, Didier Samuel5, Tarik Asselah6
1Médecine digestive, CHU ESTAING, Université d'Auvergne, Clermont Ferrand, 2Service d'Hépatogastroentérologie, CHU Limoges, Inserm UMR 1092, Limoges, 3Service d'Hépatogastroentérologie, CHU Purpan, Toulouse, France, 4Gilead Sciences, Inc., Foster City, United States, 5Centre Hepatobiliaire, Hopital Paul Brousse, Université Paris Sud , Villejuif, 6Hepatology Department, University Paris Diderot and INSERM U773, Beaujon Hospital, Clichy, France

Background and Aims: Hepatitis C virus (HCV) genotype (GT) 4 is estimated to account for 8% to 13% and GT5 for ~1% of all chronic HCV infections globally (Gower et al. 2014 J Hepatol;61:S45-S57; Messina et al. 2014 Hepatology doi: 10.1002/hep.27259). GT4 HCV is found primarily in the Middle East and Sub-Saharan Africa and GT5 HCV primarily in Southern Africa. Clinical studies evaluating the treatment outcome with new direct acting antiviral agents in GT4 and especially GT5 HCV infection have been limited. The aim of the current ongoing study is to assess the safety, tolerability and efficacy of ledipasvir/sofosbuvir (LDV/SOF) in patients with chronic GT4 or GT5 HCV infection.

Methods: Treatment-naïve and treatment-experienced patients with chronic GT4 or GT5 HCV infection were enrolled at 5 sites in France to receive 12 weeks of LDV/SOF (90 mg/400 mg daily). Up to 50% of patients could have compensated cirrhosis at screening. The primary endpoint is the SVR12 rate with SVR4 as a secondary endpoint.

Results: 85 patients were enrolled: 44 patients had GT4 and 41 patients had GT5 chronic HCV infection. Overall, GT4 patients were 64% male, mean age 51 years, 50% were treatment-experienced, 18% had IL28B-CC genotype, 23% had compensated cirrhosis, and 70% had HCV RNA ?800,000 IU/mL at baseline. Overall, GT5 patients were 51% male, mean age 63 years, 49% were treatment-experienced, 46% had IL28B CC genotype, 22% had compensated cirrhosis, and 85% had HCV RNA ?800,000 IU/mL at baseline.

SVR4 rates are shown in the Table. Complete SVR12 data will be presented.

The most common adverse events (>10% of patients) were asthenia, headache, and fatigue. Most AEs were mild or moderate in severity and none resulted in treatment discontinuation. One patient experienced an SAE of worsening of pre-existing depression which was considered unrelated to study drug. There were no grade 3 or 4 clinical laboratory abnormalities.

Conclusions: A ribavirin- and interferon-free regimen of ledipasvir/sofosbuvir administered in a fixed-dose combination tablet once daily for 12 weeks resulted in high SVR4 rates of 93% in GT4 and in GT5 HCV-infected treatment-naïve and treatment-experienced patients with or without cirrhosis. This regimen was well tolerated and represents a simple, highly effective all-oral treatment option which could facilitate more widespread treatment of patients.

Figure:

SVR4 rates (%,n/N) following LDV/SOF in GT4 and GT5 HCV infection GT4 GT5

Overall 93 (41/44) 93 (38/41)1
Treatment Naive 95 (21/22) 90 (19/21)1
Treatment Experienced 91 (20/22) 95 (19/20)

Cirrhosis 100 (10/10) 89 (8/9)
No cirrhosis 91 (31/34) 94 (30/32)

1 1 patient lost to follow-up

Disclosure of Interest: A. Abergel: Grant: Roche, Consultant: Gilead, MSD, Roche, Sponsored Lectures (National or International): Gilead, Janssen, BMS, Roche, V. Loustaud-Ratti: Grant: Gilead, BMS, Roche, Consultant: Gilead, MSD, Roche, Sponsored Lectures (National or International): Gilead, Janssen, BMS, Roche, Merck/Schering Plough, S. Metivier: : None Declared, D. Jiang: Stockholder: Gilead, Employee: Gilead, K. Kersey: Stockholder: Gilead, Employee: Gilead, S. Knox: Stockholder: Gilead, Employee: Gilead, P. Pang: Stockholder: Gilead, Employee: Gilead, D. Samuel: Consultant: Gilead, MSD, BMS, Abbvie, T. Asselah: Grant: Gilead, AbbVie, BMS, Janssen, Roche, MSD, Consultant: Gilead, AbbVie, BMS, Janssen, Roche, MSD

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